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Vaping and Disease Risks Cynthia Grondin, PhD Comparative Toxicogenomics Database North Carolina State University 11/12/2019

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Page 1: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Vaping and Disease Risks

Cynthia Grondin, PhDComparative Toxicogenomics Database

North Carolina State University11/12/2019

Page 2: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

e-liquid

mouthpiece

on/off switch

Lithium battery

atomizer

Vape mods

aerosol/vapor

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 3: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

common e-cigarette vaping devices

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 4: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Juuls – “Juuling”

1 pod = nicotine in entire pack of cigarettes

ALL Juuls contain NICOTINE

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 5: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Anatomy of a Juul

mouthpiece

chimney

gold plated contact

coil, wick

indicator

e-liquid

battery

e-vapor

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 6: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Beyond the List of Ingredients

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

Juul chemicals

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

biotransformation of nicotine into other compounds

Pharmacological Reviews 57(1):79–115

Page 7: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

conversion of propylene glycol into acetaldehyde and formaldehyde (carcinogens)

Environ Sci Technol 50(17):9644-9651

Juul chemicals

Beyond the List of Ingredients

Page 8: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

conversion of glycerin into acrolein (carcinogen)

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Environ Sci Technol 50(17):9644-9651

Juul chemicals

Beyond the List of Ingredients

Page 9: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

glycerol

propylene glycol

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

PLoS ONE 12(3):e0173055

benzoic acid can transform into benzene (carcinogen)Juul chemicals

Beyond the List of Ingredients

Page 10: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

nicotinepropylene glycolglycerinbenzoic acidflavorings, oils

1-hexanol cyclotene limonene

2,3-pentanedione decan-4-olide linalool

2,5-dimethylpyrazine decanaldehyde linalyl acetate

2,6-lutidine Diacetyl maltol

2-acetylpyrrole diethyl succinate Menthol

3,4-dihydrocoumarin ethyl acetoacetate menthone

3-hexen-1-ol ethyl hexanoate methyl acetate

4-Butyrolactone ethyl lactate methyl cinnamate

5-methyl-2-furfural ethyl maltol methyl salicylate

acetoin Ethyl Salicylate methylheptenone

alpha-terpineol ethyl vanillin Nicotine

anisyl acetate Eucalyptol n-pentanol

benzaldehyde Eugenol Pulegone

benzyl acetate Furaldehyde pyridine

Benzyl Alcohol furaneol raspberry ketone

Camphor furfuryl alcohol tetramethylpyrazine

Cinnamaldehyde gamma-valerolactone vanillin

citronellol isoamyl acetate

Alien Blood Double Apple Hookah Oatmeal Cookie

Bad Apple Energy Drink Orange Mint

Bluewater Punch Grape Hookah Peach Schnapps

Carmel Popcorn Iced Berry Pina Colada

Cherry Lava Java Jolt Pomegranate

CooCoo Coconut Just Guava Snap!

Cotton Candy Kick! Tutti Frutti

Cupcake Menthol Vanilla Bean

flavorings may contain many other chemicals such as Diacetyl(shown to cause Popcorn Lung)

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Juul chemicals

Beyond the List of Ingredients

Page 11: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Universal System for Analysis of Vaping (U-SAV) machine

What chemicals are in e-liquids and aerosols?

Int J Environ Res Public Health 14(10): 1225

chemicals are measured in e-liquids, aerosols, urine, blood, saliva

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 12: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Vaping is NOT just inhaling flavored water vapor

PLoS One. 2013;8(3):e57987

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 13: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Metals contaminate e-liquids and aerosols

Environ Health Perspect. 2018 Feb 21;126(2):027010

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 14: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

propylene glycol

glycerol

benzoic acid

glycerin

benzeneacrolein

glycidol

propionaldehyde

1-hexanol

anisyl acetategamma-valerolactone

5-methyl-2-furfural

4-butyrolactone

acetoin

decanaldehyde

methylheptanone

maltol

Eugenolethyl acetoacetate

2,3-pentanedionedecanaldehyde

furaldehyde

limonene

benzyl acetate

Menthol

cyclotene

Diacetyl

vanillin

1-hexanol3,4-dihydrocourmarin

methyl salicylate

Pulegone

camphor

alpha-terpineol

3-hexen-1-ol

pyridine

2-acetylpyrrole

2,6-lutidine

Nicotine

Free Radicals

methylglyoxal

2-butenal

Particulate Matter

Acetone Acetaldehyde

Formaldehyde

Aluminum

Nickel

Lead

ZincManganese

Tin

Chromium

Copper

Iron

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Vaping aerosols contain MANY chemicalsmany more than shown here

Page 15: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Diseases

Chemicals

Genes

GO &

Phenotype

Comparative Toxicogenomics

Database (CTD)

Integrate data

Exposures

Pathways

ctdbase.org

• >43 million

toxicogenomic

relationships

• updated monthly

Cellular locationMolecular functionBiological processes

PhD-level scientists

read studies

Health Effects of Chemicals

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 16: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

ctdbase.org

Chemicals Diseasesdirect

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 17: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

ctdbase.org

Chemicals Diseases

Genes

inferred

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 18: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Nicotine (Protonated) vs Nicotine (Free base) vs Salts

Nic[H+] Nic

• acidic environment low pH• protonated• does not cross membranes

rapidly• less potent• deposits in respiratory tract

~50% efficiency• tobacco smoke • ~ 12mg/cigarette

• deprotonated/free base• more volatile• more potent• harsher throat hit• increased sensory effects• rapidly deposits in mouth,

respiratory tract• e-cigarettes• ~0-24 mg/ml

Nicotine Salts

• nicotine benzoate• nicotine levulinate• nicotine pyruvate• rapid absorption

• JUULs• smoother throat hit

• allows higher nicotine

• ~60 mg/ml

flavors can affect pH of e-liquids and consequently, nicotine form

+

-

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 19: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Effects of Nicotine in e-cigarette aerosol

interacts with 1,128 unique genes

Nicotine

involved in 2,656 gene interactions

involved in 631 molecular pathways

associated with 934 phenotypes

directly related to 224 diseases

inferred relationship to 1,837 diseases

Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 20: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Nicotine Effects on HealthNicotine-DiseasesNicotine-Disease Categories

• Cardiovascular Disease• Respiratory Tract Diseases• Reproductive Disorders• Depression• Lung Cancer• Colon Cancer• Type 2 Diabetes• Pulmonary Fibrosis• Pancreatic Cancer• Heart Attack• Nerve Degeneration• Atherosclerosis• Stroke• Metastasis• Acute Kidney Injury• Hypertension• Panic Disorder

224 direct/1837 inferred disease relationships

Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 21: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Chemical-Disease Associations in CTD

Input chemicals in e-liquids/aerosols

Search for disease associations

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 22: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Chemicals in Juul pods and aerosols

• Nervous System • Cardiovascular • Respiratory Tract

• Cancer• Immune System• Mental Disorders

Top Disease Categories

Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 23: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Vaping-Related Illness aired on GMA 9/3/2019

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 24: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health

Comparative Toxicogenomics Database

Number of Lung Injury Cases Reported to CDC as of November 5, 2019

Page 25: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Centers for Disease Control Updates

November 8, 2019

• 2,051 vaping-related illnesses across 49 states

• 39 confirmed deaths related to vaping, in 24 states

• more deaths under investigation

• chemical of concern vitamin E acetate

October 15, 2019 (867 patients)

• 86% reported vaping THC (34% THC exclusively)

• 64% reported vaping nicotine (11% nicotine exclusively)

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 26: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Scientific Study on Vaping Cannabis

• cannabis smoke contains many of the same carcinogens found in

tobacco smoke

• average particle concentrations of 200-600 ug/m3, peak concentrations

1600 mg/m 3

• equivalent to extreme air pollution (wildfires and severe industrial

pollution)

• can cause cardiovascular and respiratory disease

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Measuring Aerosol Particulate Emissions from Cannabis Vaporization and Dabbing

Jacques PA, Zalay M, Huang A, Jee K, Schick S [email protected]

Page 27: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Vaping THC - Concerns

1) Pesticides and Solvents

i. pesticides and fungicides used to grow cannabis

ii. concentration solvents (butane, hexane, isobutene, isopropyl alcohol)

2) Flavorings added to cannabis products

i. Diacetyl, 2,3-Pentanedione, Acetoin

3) Cutting agents

i. Vitamin E acetate

Borodovsky JT. Addiction http://doi.org/10.1111.add.14855

Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 28: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Vitamin E Analogues

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

I II III

functional group

signalingdomain

hydrophobic domain

a-Tocopheryl Acetate

Br J Cancer. 2003. 88: 1948-1955

Page 29: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

THC Effects on HealthTHC-Disease AssociationsTHC-Disease Categories• Substance-related Disorders• Nerve Degeneration• Morphine Dependence• Bipolar disorder• Marijuana Abuse• Acute Kidney Injury• Anxiety Disorders• Hypotension• Cognition Disorders• Opioid Disorders• Pregnancy Complications• Movement Disorders• Memory Disorders• Learning Disorders• Tachycardia• Catalepsy• Pulmonary Edema

87 direct/2874 inferred disease relationships

Cynthia J Grondin, PhD 11/12/2019Illuminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 30: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

e-cig vapor S. mutans

Kim et al. PLoS One 2018 Sept 7

Vaping Effects on Teeth

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 31: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

More Immediate Effects?

Nicotine is HIGHLY addictive

Increases likelihood of smoking cigarettes

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 32: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Acrolein, nicotine and other vaping chemicals may contribute to a hardening of the arteries and limit cardiovascular fitness

Effects on Cardiovascular Fitness:

More Immediate Effects?

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 33: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Effects on Mental Health:Adolescent e-cigarette users show increased Depression, Panic Disorder and inability to experience pleasure vs. non-users

More Immediate Effects?

Vaping associated with illicit drug use, mental health problems and impulsivity in university students

Leventhal AM et al. J Psychiatr Res. 2016 FebGrant JE et al. Ann Clin Psychiatry 2019 Feb

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 34: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Effects on Sexual Health:

Nicotine can significantly decrease physiological sexual arousal in healthy nonsmoking men and women (18-22 years)

More Immediate Effects?

J Sex Med. 2008 Jan;5(1):110-21J Sex Med. 2008 May; 5(5):1184-1197

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 35: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Chen et al., J Expo Sci Environ Epidemiol. 2017 Dec 29

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Second-hand and Third-hand Vape

Page 36: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Vaping Affects Users Differently

• type of device

• e-liquid

• vaping patterns

• coil resistance, age, composition

• user age, weight, metabolism, health,

genetics

• environmental factors

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 37: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

Combustible vs. E-cigarettes

Both increase risks of adverse health outcomes

Both expose users to toxic chemicals (smoke and e-vapor)

Vaping increases risk of smoking tobacco cigarettes

Exposure to toxic substances from combustible tobacco cigarettes may be greater than from e-cigarettes

Exposure to metals (e.g., lead, nickel, chromium) may be greater in e-cigarette vapor than tobacco cigarettes

Both are addictive

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 38: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

E-liquids AND aerosols contain toxic chemicals

Vaping chemicals can cause DNA damage

Vaping impacts genes, pathways, immune system

Vaping negatively impacts physical and mental health

Vaping increases risk of thousands of diseases

Take Home Points

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 39: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

The New Look of Nicotine Addiction (Massachusetts Tobacco Cessation & Prevention Program)

– www.GetOutraged.org

Surgeon General: E-Cigarettes & Young People– www.e-cigarettes.surgeongeneral.gov/

Centers for Disease Control: Electronic Cigarettes– https://www.cdc.gov/tobacco/basic_information/e-

cigarettes/index.htm

Educate Yourself

Resources for HELP

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database

Page 40: Vaping and Disease Risks - HoneyHole... · 12/11/2019  · E-liquids AND aerosols contain toxic chemicals Vaping chemicals can cause DNA damage Vaping impacts genes, pathways, immune

.ORG

Cynthia J Grondin, PhDIlluminating how chemicals affect human health

Comparative Toxicogenomics Database